PubMed Health⌕ Search

Biomedical subjects

D C Hoffman

Publications and source records attributed to D C Hoffman.

At least 37 records · Page 2Linked to original sources
PubMed1993

Lack of cross-sensitization between the locomotor-activating effects of bromocriptine and those of cocaine or heroin.

Rats were given daily injections of bromocriptine (5.0 mg/kg IP) or vehicle either in the home cage or in a test box equipped with photocells to measure locomotion. The animals were then tested in the photocell boxes for their locomotor response to cocaine (10.0 mg/kg IP), heroin (0.5 mg/kg IP), or quinpirole (0.1 mg/kg IP). Repeated bromocriptine in the test box but not in the home cage caused progressive increases in sensitivity to the locomotor-stimulating effects of bromocriptine and increases in the subsequent sensitivity to quinpirole but caused only trivial signs of cross-sensitization to cocaine or heroin. Cross-sensitization to quinpirole was temporary; responsiveness to quinpirole decreased with further quinpirole injections. Lack of significant cross-sensitization between bromocriptine and either cocaine or heroin and lack of permanence of the cross-sensitization between bromocriptine and quinpirole raise questions as to the biological basis of psychomotor stimulant sensitization.

Animals↗
PubMed1993

The effects of haloperidol and clozapine on the disruption of sensorimotor gating induced by the noncompetitive glutamate antagonist MK-801.

The amplitude of the acoustic startle response in rats is decreased if the startle stimulus is preceded by a nonstartle-eliciting auditory stimulus. This sensory gating phenomenon, known as prepulse inhibition, is diminished in schizophrenic individuals. In rats, the noncompetitive glutamate antagonist MK-801 disrupts prepulse inhibition. The present study examined whether the disruption by MK-801 is reversible in rats pretreated with the classical antipsychotic haloperiodol or the atypical antipsychotic clozapine. Male Sprague-Dawley rats were placed into a startle chamber and presented with auditory stimuli consisting of either 95 or 105 dB tones presented alone or preceded by a 70 dB tone. Rats treated with 0.1 mg/kg MK-801 demonstrated a significant disruption of prepulse inhibition. Haloperidol (0.1 and 0.5 mg/kg) and clozapine (1.0 and 5.0 mg/kg) each consistently failed to antagonize the MK-801-induced blockade of prepulse inhibition. The effects of haloperidol and clozapine on prepulse inhibition were also examined in saline-treated rats. Clozapine and, to some extent, haloperidol produced a dose-related facilitation of prepulse inhibition. Although preliminary, this finding raises the possibility that the enhancement of prepulse inhibition by antipsychotics might provide a useful rodent model for screening potential antipsychotic drugs.

Acoustic Stimulation↗
PubMed1992

Localization of drug reward mechanisms by intracranial injections.

Intracranial drug injections are useful in localizing brain areas where drugs of abuse initiate their habit-forming actions. However, serious methodological problems accompany such studies. Pharmacological controls are necessary to assess non-receptor-mediated local actions of the drug, anatomical controls are necessary to rule out drug efflux to distal sites of action, and behavioral controls are necessary to separate rewarding from general activating effects of drugs. Five brain sites have been advanced as sites of rewarding opiate actions: the ventral tegmental area (VTA), nucleus accumbens septi (NAS), lateral hypothalamus, periaqueductal gray, and hippocampus. Current evidence appears to confirm two of these--VTA and NAS; evidence is currently incomplete in the case of the hippocampus and is conflicting in the case of the lateral hypothalamus and periaqueductal gray. Two sites have been advanced as sites of rewarding psychomotor stimulant actions: NAS and the frontal cortex; each site seems implicated, but puzzling differences between amphetamine and cocaine findings remain to be resolved. Each of the clearly implicated sites is local to dopamine cell bodies or dopamine terminals that have been implicated in the rewarding effects of brain stimulation, food, and sex.

Animals↗
PubMed1992

Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats.

The effects of typical and atypical neuroleptics on MK-801-induced locomotor activity and stereotyped sniffing were tested. Pretreatment with the typical neuroleptic haloperidol (0.01, 0.05, 0.1, 0.5 mg/kg SC) and the dopamine D2 receptor selective antagonist eticlopride (0.005, 0.01, 0.05 mg/kg SC) each resulted in significant and dose-dependent reductions of locomotor activity and sniffing. The atypical neuroleptic clozapine (1.0, 5.0, 10.0 mg/kg SC) was somewhat unique in that all doses reduced locomotor activity, but only the highest dose (10.0 mg/kg) significantly reduced sniffing. The data support a functional interaction between glutamate and dopamine systems, and suggest that the behavioral activation associated with MK-801 may represent a valid model for detecting potential therapeutic agents in the treatment of schizophrenia. The data should be viewed as preliminary, however, until neuroleptics are characterized in other glutamate-based models that minimized or exclude the possible influence of nonspecific motor effects.

Animals↗
PubMed1992

Locomotor-activating effects of the D2 agonist bromocriptine show environment-specific sensitization following repeated injections.

Biphasic effects of bromocriptine (2.0, 5.0, 10.0, and 20.0 mg/kg IP) on locomotion were quantified in photocell activity boxes in rats. Following early suppression of activity, bromocriptine produced a clear, dose-dependent increase in locomotion that lasted several hours. When a low dose of bromocriptine (5.0 mg/kg) was administered daily over a 3-week period, the locomotor-activating effects of the drug showed progressive enhancement over days. The sensitization was environment specific; rats administered bromocriptine six times in the home cage showed no sign of a sensitized response to bromocriptine when subsequently tested in the activity box. Thus, selective stimulation of D2 receptors stimulates locomotion and sensitizes animals to subsequent injections, just as do the indirect-acting dopamine agonists cocaine and amphetamine.

Animals↗
PubMed1991

Ventral pallidal microinjections of receptor-selective opioid agonists produce differential effects on circling and locomotor activity in rats.

Locomotor activity was investigated following microinjections of receptor-selective opioid agonists into the ventral pallidum (VP) of rats. In Expt. 1, male Long-Evans rats were treated with unilateral microinjections of the mu agonist [D-Ala2-MePhe4, Gly-ol5]-enkephalin (DAGO), the delta agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) or the kappa agonist U50,488H, and the rate and duration of circling behaviour were measured. DAGO (0.01, 0.1, 1.0 nmol) produced a dose-dependent increase in contralateral circling; pretreatment with 1.0 mg/kg naltrexone blocked the circling induced by the highest dose. The behavioral effect was largest when injections were targeted at the VP rather than structures dorsal to the VP. In contast to DAGO, intrapallidal DPDPE (0.01, 0.1, 1.0, 10.0 nmol) produced a slight increase in contralateral circling only at the highest dose and U50, 488H (0.01, 0.1, 1.0, 10.0 nmol) produced no effect. In Expt. 2, the effects of bilateral injections of DAGO, DPDPE and U50,488H were tested in photocell activity boxes. DAGO produced a dose-dependent increase in locomotor activity and this increase was decreased by 1.0 mg/kg naltrexone. A slight increase in activity was observed with the highest dose of DPDPE, and a slight decrease was observed with the highest dose of U50,488H. These findings confirm that opiate actions in the VP contribute to opiate-induced locomotion and suggest that mu and to some extent delta receptors are involved in this behavior.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Preferential stimulation of D1 or D2 receptors disrupts food-rewarded operant responding in rats.

Rats were trained to lever-press for food on a variable interval 30-sec schedule. Following stabilization of response rates, separate groups of rats were treated with saline, the nonselective DA agonists amphetamine or apomorphine, the D1 agonist SKF 38393, or the D2 agonist quinpirole prior to placement in the operant chamber. Treatment with SKF 38393 or quinpirole produced dose-dependent reductions in overall response rates which were similar to those observed with either amphetamine or apomorphine. In addition, treatment with the D2 agonist produced a gradual decline in responding within each test session. These data suggest that preferential stimulation of either D1 or D2 receptors is sufficient in disrupting food-reinforced lever-pressing; furthermore, the extinction-like intrasession decline in responding induced by the D2 agonist suggests that this drug, unlike the others, may have disrupted responding by reducing the reinforcing efficacy of the food.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

The effects of selective dopamine D1 or D2 receptor antagonists on the establishment of agonist-induced place conditioning in rats.

The ability of the dopamine D1 antagonist, SCH 23390 (0.01, 0.1, 1.0, 2.0 mg/kg) or the D2 antagonist, metoclopramide (1.0, 10.0, 20.0 mg/kg), to block the establishment of place conditioning with either the nonselective dopamine agonist, amphetamine (2.0 mg/kg), the D1 agonist, SKF 38393 (10.0 mg/kg), or the D2 agonist, quinpirole (1.0 mg/kg), was evaluated in rats. The experimental protocol consisted of three phases. During the preexposure phase, rats explored two distinctive compartments joined by a small tunnel. During the 8-day conditioning phase, rats were pretreated with either saline, SCH 23390 or metoclopramide; 1 hr later the animals were treated with an agonist and confined to one compartment for 30 min. On alternate days, rats received saline and were placed in the opposite compartment. Test days occurred over the remaining 3 days during which drug-free animals were allowed access to both compartments. A significant increase or decrease in the amount of time spent in the drug-paired environment was indicative of a place preference or aversion, respectively. SCH 23390 and metoclopramide were effective in blocking amphetamine-induced place preference and SKF 38393-induced place aversion. At lower doses, the D1 and D2 antagonist blocked the place preference induced by quinpirole, however, higher doses were not effective. In general, these data suggest that both receptor subtypes participate in the establishment of place conditioning with amphetamine, SKF 38393 or quinpirole.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Selective D1 and D2 dopamine agonists produce opposing effects in place conditioning but not in conditioned taste aversion learning.

The neurotransmitter, dopamine (DA), has been implicated in place conditioning but the role of D1 and D2 receptors has not been investigated. In Experiment 1, the effects of SKF 38393 (0, 0.01, 0.1, 1.0, 10.0 mg/kg) and quinpirole (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg), preferential D1 and D2 receptor agonists, respectively, were evaluated and compared to (+)-amphetamine (0, 0.01, 0.1, 1.0, 2.0, 4.0 mg/kg). The experiment consisted of three phases. During the preexposure phase, rats explored two distinctive end compartments adjoined by a small tunnel. The time spent in each compartment was recorded. During the 8-day conditioning phase, rats were treated with drug and confined to one compartment for 30 min. On alternate days, rats received saline and were placed in the opposite compartment. Test days occurred over the remaining three days during which drug-free animals explored both compartments. Rats conditioned with (+)-amphetamine demonstrated a dose-dependent increase in time spent in the drug-paired environment from preexposure to test indicating the establishment of a conditioned place preference. Treatment with quinpirole also resulted in a conditioned place preference, however, only an intermediate dose was effective. In contrast, SKF 38393 produced a dose-dependent decrease in time spent on the drug-paired side suggesting the establishment of a place aversion. The idea that D1 receptors may be exclusively involved in mediating the aversive properties of psychomotor stimulants was tested in Experiment 2 employing a conditioned taste aversion paradigm. The results did not support this notion; it was found that both quinpirole and SKF 38393 produced a conditioned taste aversion.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

The dopamine D2 receptor agonists, quinpirole and bromocriptine produce conditioned place preferences.

1. The conditioned place preference paradigm was used to examine the role of the D2 receptor in mediating the reinforcing effects of dopamine (DA) agonists. 2. During the 3-day pre-exposure phase, rats explored two distinctive end compartments which were adjoined by a small tunnel. During the 8-day conditioning phase, groups of rats were treated with the selective D2 receptor agonists, quinpirole (0.01, 0.025, 0.05, 0.10, 0.25, 1.0 and 5.0 mg/kg IP) or bromocriptine (0, 0.01, 0.1, 0.5, 1.0, 5.0 and 10.0 mg/kg IP) and confined to one compartment for 30 min. On alternate days, rats received vehicle injections and were placed in the opposite compartment. Test days occurred over the remaining 3 days during which untreated animals explored both compartments. 3. Rats conditioned with quinpirole or bromocriptine showed significant increases in time spent in the drug-paired environment from pre-exposure to test indicating the establishment of conditioned place preferences. 4. This suggests a functional role for the D2 receptor in mediating the rewarding effects of DA agonists.

Animals↗
PubMed1987

Effects of extinction, pimozide, SCH 23390, and metoclopramide on food-rewarded operant responding of rats.

The similarity in the pattern of responding produced by extinction and dopamine (DA) receptor blockers has led to the suggestion that DA neurons may participate in the usual effects of reward on behaviour. The purpose of the present study was to evaluate the effect of receptor-subtype specific DA antagonists on food-rewarded operant responding. Rats were trained to lever press for food on a variable interval 30-s schedule. They then received one of the following treatments prior to testing on the next 5 days: saline, nonreinforcement, the DA receptor blocker pimozide (0.5 or 1.0 mg/kg), the D1 receptor blocker SCH 23390 (0.01, 0.05, 0.1 mg/kg), and the D2 receptor blocker metoclopramide (1.0, 5.0, 10.0 mg/kg). Nonreinforcement resulted in both intra- and intersession declines in responding. The drugs produced dose-dependent decreases in overall responding. Additionally, both doses of pimozide and the higher doses of SCH 23390 and metoclopramide altered intrasession patterns of responding when compared to saline, with their greatest effect being in the latter portion of the session. Intersession declines were seen with the highest doses of SCH 23390 and metoclopramide and control studies showed that these declines could not be attributed to a buildup of the drug with repeated dosing. It was concluded that both D1 and D2 receptors participate in the control of behaviour by reward.

Animals↗
PubMed1986

Feeding behavior in rats is differentially affected by pimozide treatment depending on prior experience.

It has been observed in previous research that rats treated with the dopamine receptor antagonist, pimozide, failed to eat palatable food pellets. Two possible interpretations for this effect were evaluated, namely, a reduction in the primary level of food motivation or drug-induced hypokinesia resulting in a subsequent failure to find the food. The effects of several doses of pimozide (1.0, 2.0 and 4.0 mg/kg IP) on feeding in rats with or without experience eating food pellets in an experimental chamber were tested. Pimozide had little effect on feeding in rats with prior experience whereas the drug produced a dose-dependent impairment in rats without similar experience. In addition, although the initial impairment was severe, the nonexperienced rats became more efficient at locating the food despite pimozide treatment. These results appear to rule out a primary motivational interpretation for the effect of pimozide on feeding; rather, the impairment is likely due to the drug's hypokinesia-producing properties.

Animals↗
PubMed1986

Use of direct sagittal computed tomography in diagnosis and treatment of internal derangements of the temporomandibular joint.

Direct sagittal CT imaging of the TMJ provides several distinct advantages. Most significant is that direct imaging allows noninvasive evaluation of the disk. Direct sagittal CT scanning can confirm a clinical diagnosis of internal derangements as well as monitor splints intended for recapturing of the disk. Furthermore, the CT direct imaging allows excellent views of the bony architecture similar to those obtained with tomography. Used with clinical history and physical examination, CT can provide an excellent diagnostic modality to help provide better care for patients with internal derangement of the TMJ.

Adult↗
PubMed1986

On the use of a bubble formation model to calculate diving tables.

Previous decompression tables for humans were based upon unsupported assumptions because the underlying processes by which dissolved gas is liberated from blood and tissue were poorly understood. Some of those assumptions are now known to be wrong, and the recent formulation of a detailed mathematical model describing bubble nucleation has made it possible to calculate diving tables from established physical principles. To evaluate this approach, a comprehensive set of air diving tables has been developed and compared with those of the U.S. and British Navies. Conventional decompressions, altitude bends, no-stop thresholds, and saturation dives are all successfully described by one setting of four global nucleation parameters, which replace the U.S. Navy's matrices of M-values. Present air diving tables show great irregularity, even within sets created by the same authors. In contrast, this new approach is remarkably self-consistent, permitting accurate interpolation and extrapolation.

Biophysical Phenomena↗
PubMed1985

The effects of pimozide on the establishment of conditioned reinforcement as a function of the amount of conditioning.

In an attempt to understand some inconsistent findings, the present experiment investigated the effects of pimozide, a dopamine (DA) receptor blocker, on the establishment of conditioned reinforcement as a function of the amount of conditioning. In Experiment 1, rats received three phases of training in a two-lever box. The pre-exposure phase measured the operant rates of pressing the levers; one produced a 3-s tone and the other turned the lights off for 3 s. In the conditioning phase, with the levers absent, the light-off stimulus was paired with food for two or four sessions. The test phase again measured the rate of pressing the levers. Conditioned reinforcement was shown by a relative increase in responding on the light lever during the test. Of the groups receiving four conditioning sessions, pimozide (0.5, 1.0, 2.0 and 4.0 mg/kg) produced a dose-dependent attenuation of conditioned reinforcement, those rats treated with 4.0 mg/kg failing to demonstrate a significant effect. When 2 conditioning days were employed, pimozide treatment also produced a dose-dependent attenuation; however, in these less conditioned animals 2.0 mg/kg blocked the effect. The possibility that pimozide produced a conditioned taste aversion to the food was ruled out in Experiment 2. These data suggest that DA transmission may be necessary for the establishment of conditioned reinforcement and that the effects of receptor blockade may be related to the amount of conditioning.

Animals↗
PubMed1985

The D1 dopamine receptor antagonist, SCH 23390 reduces locomotor activity and rearing in rats.

Dopamine receptors have been found to be of at least two types, and interest has focused on the possible differential role played by each in the control of behavior. The recent finding that SCH 23390 selectively blocks D1 receptors has provided a new tool. To examine the contribution of D1 receptors to locomotor activity and rearing, rats were injected SC with doses of 0.01, 0.1 and 1.0 mg/kg and monitored for 3 hr in photocell cages. SCH 23390 suppressed both behaviors in a dose-dependent fashion. These results suggest that D1 receptors participate in dopamine's control of locomotor activity and rearing.

Animals↗